Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

Longqing Zhang; Xi Tan; Fanhe Song; Danyang Li; Jiayi Wu; Shaojie Gao; Jia Sun; Daiqiang Liu; Yaqun Zhou; Wei Mei

doi:10.4103/1673-5374.380905

Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

Neural Regen Res. 2024 Mar;19(3):687-696. doi: 10.4103/1673-5374.380905.

Authors

Longqing Zhang¹, Xi Tan¹, Fanhe Song¹, Danyang Li¹, Jiayi Wu¹, Shaojie Gao¹, Jia Sun¹, Daiqiang Liu¹, Yaqun Zhou¹, Wei Mei¹

Affiliation

¹ Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Abstract

Activated G-protein-coupled receptor 39 (GPR39) has been shown to attenuate inflammation by interacting with sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). However, whether GPR39 attenuates neuropathic pain remains unclear. In this study, we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats. Intrathecal injection of TC-G 1008, a specific agonist of GPR39, significantly alleviated mechanical allodynia in the rats with spared nerve injury, improved spinal cord mitochondrial biogenesis, and alleviated neuroinflammation. These changes were abolished by GPR39 small interfering RNA (siRNA), Ex-527 (SIRT1 inhibitor), and PGC-1α siRNA. Taken together, these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1α pathway in rats with spared nerve injury.

Keywords: G-protein-coupled receptor 39 (GPR39); mitochondrial transcription factor A (TFAM); neuroinflammation; neuropathic pain; nuclear respiratory factor 1 (NRF1); peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α); sirtuin 1 (SIRT1); spinal cord.